Drug Interactions Between Voriconazole and Atazanavir Coadministered as Atazanavir/Ritonavir in Healthy Participants

This study has been completed.

Sponsor:

Bristol-Myers Squibb

ClinicalTrials.gov Identifier:

NCT00833482

First Posted: February 2, 2009

Last Update Posted: October 25, 2012

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
Read our disclaimer for details.

Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Atazanavir, Administered as Atazanavir/Ritonavir With and Without Voriconazole, in Participants Who Are Extensive Metabolizers (EM) [ Time Frame: Predose and at 1, 2, 3, 4, 5, 7, 9,13, and 24 hours postdose on Days 20 and 30 of a 30-day cycle ]

EM participants are those with functional CYP2C19 alleles.

Time to Maximum Concentration (Tmax) of Atazanavir, Administered as Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants [ Time Frame: Predose and at 1, 2, 3, 4, 5, 7, 9,13, and 24 hours postdose on Days 20 and 30 of a 30-day cycle ]

Area Under the Plasma Concentration-time Curve in 1 Dosing Interval [AUC(TAU)] of Atazanavir Administered as Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants [ Time Frame: Predose and at 1, 2, 3, 4, 5, 7, 9,13, and 24 hours postdose on Days 20 and 30 of a 30-day cycle ]

Tmax of Voriconazole, Administered With and Without Atazanavir/Ritonavir, in EM Participants [ Time Frame: Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdoseDays 3 and 30 of a 30-day cycle ]

Cmax and Cmin of Voriconazole, Administered With and Without Atazanavir/Ritonavir, in EM Participants [ Time Frame: Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdoseDays 3 and 30 of a 30-day cycle ]

Cmax and Cmin of Ritonavir, Administered As Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants [ Time Frame: Predose and at 1, 2, 3, 4, 5, 7, 9,13, and 24 hours postdose on Days 20 and 30 of a 30-day cycle ]

Tmax of Ritonavir, Administered As Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants [ Time Frame: Predose and at 1, 2, 3, 4, 5, 7, 9,13, and 24 hours postdose on Days 20 and 30 of a 30-day cycle ]

AUC(TAU) of Ritonavir, Administered As Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants [ Time Frame: Predose and at 1, 2, 3, 4, 5, 7, 9,13, and 24 hours postdose on Days 20 and 30 of a 30-day cycle ]

Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Any AE [ Time Frame: Days 1 to 31 (discharge), continuously ]

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.

Number of Participants With Marked Abnormalities in Serum Chemistry Test Results [ Time Frame: Within 21 days of Day 1 and on Days 3, 10, 20, 26, and 31 (at discharge) ]

LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Safety criteria: AST and ALT: If >1.25*ULN, or if preRX>ULN, use >1.25*preRX. Total and direct bilirubin: If >1.1*ULN or if preRX>ULN, use >1.25*preRX. Creatinine: If >1.33*preRX. Serum glucose, fasting: If preRX<LLN, use <.8*preRX or >ULN; if preRX>ULN, use >2*preRX or <LLN. Creatinine kinase: If >1.5*ULN or preRX>ULN, use >1.5*or preRX. Lactose dehydrogenase: If >1.25*ULN or preRX>ULN, use >1.5*preRX.

Number of Participants With Marked Abnormalities in Hematology Laboratory Test and Urinalysis Results [ Time Frame: Within 21 days of Day 1 and on Days 3, 10, 20, 26, and 31 (at discharge) ]

LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Safety criteria: Neutrophils + bands: If <.85*LLN or >1.15*ULN or ULN or if preRX<LLN, use <0.85*preRX or >ULN; if preRX>ULN, use >1.15*preRX or <LLN. Lymphocytes, relative: If <0.85*LLN or >1.15*ULN, or if preRX <LLN, use <0.85*preRX or >ULN; if preRX >ULN, use >1.15*preRX or <LLN. Blood, urine: If >= 2+, or if preRX >=1+, use >=2*preRX. White blood cells, urine: If >=2+, or if preRX >=2+, use >=4+. Red blood cells, urine: If >=2+ or if preRX >=2+, use >=4+. Not all categories were evaluated for each arm.

Number of Participants With Investigator-identified Abnormalities in Electrocardiogram Results Not Present Prior to Administration of Study Drug and Considered Not Relevant and Not AEs by Investigator [ Time Frame: Within 21 days of Day 1 and on Days -1, 21, and 31 (at discharge) ]

volt=voltage; LVH=left ventricular hypertrophy

Number of Participants With Abnormalities in Vital Signs [ Time Frame: Within 21 days of Day 1 and on Days -1, 1, 3, 11, 21, and 31 (at discharge) ]

Treatment B: EM participants received atazanavir/ritonavir, 300/100 mg once daily (QD), on Days 11 through 20. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal.

Treatment C: EM participants received atazanavir/ritonavir, 300/100 mg QD, plus voriconazole, 400 mg BID on Day 21 then 200 mg BID on Days 22-30. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal, and 1 hour before voriconazole morning dose.Treatment E: PM participants received atazanavir/ritonavir, 300/100 mg QD plus voriconazole, 100 mg BID, on Day 21, then 50 mg BID on Days 22-30. Treatment B in PM participants: PM participants received atazanavir/ritonavir, 300/100 mg QD, on Days 11 through 20. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal.

Treatment B: EM participants received atazanavir/ritonavir, 300/100 mg once daily (QD), on Days 11 through 20. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal.

Treatment C: EM participants received atazanavir/ritonavir, 300/100 mg QD, plus voriconazole, 400 mg BID on Day 21 then 200 mg BID on Days 22-30. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal, and 1 hour before voriconazole morning dose.Treatment E: PM participants received atazanavir/ritonavir, 300/100 mg QD plus voriconazole, 100 mg BID, on Day 21, then 50 mg BID on Days 22-30. Treatment B in PM participants: PM participants received atazanavir/ritonavir, 300/100 mg QD, on Days 11 through 20. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal.

Active Comparator: Voriconazole, 50 mg BID (PM)

Drug: Voriconazole

Treatment A: Participants with functional CYP2C19 alleles (EM) received oral tablets of voriconazole, 400 mg, twice daily (BID), on Day 1, then 200 mg BID on Days 2 and 3. Voriconazole dose was given at least 1 hour after a light meal. Treatment C: EM participants received atazanavir/ritonavir, 300/100 mg once daily (QD), plus voriconazole, 400 mg BID on Day 21 then 200 mg BID on Days 22-30. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal, and 1 hour before voriconazole morning dose. Treatment E: PM participants received atazanavir/ritonavir, 300/100 mg QD plus voriconazole, 100 mg BID, on Day 21, then 50 mg BID on Days 22-30.

Treatment B: EM participants received atazanavir/ritonavir, 300/100 mg once daily (QD), on Days 11 through 20. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal.

Treatment C: EM participants received atazanavir/ritonavir, 300/100 mg QD, plus voriconazole, 400 mg BID on Day 21 then 200 mg BID on Days 22-30. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal, and 1 hour before voriconazole morning dose.Treatment E: PM participants received atazanavir/ritonavir, 300/100 mg QD plus voriconazole, 100 mg BID, on Day 21, then 50 mg BID on Days 22-30. Treatment B in PM participants: PM participants received atazanavir/ritonavir, 300/100 mg QD, on Days 11 through 20. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal.

Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:

18 Years to 45 Years (Adult)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Criteria

Inclusion Criteria:

Healthy participants as determined by no clinically significant deviation from normal